It is well known that, by intake of marijuana, various psychiatric or neurological reactions such as confusion of temporal or space sense, euphoria, alteration of memories, analgesia, hallucination and the like would be produced. The compounds generally referred to as “cannabinoid” including 9-tetrahydrocannabinol (9-THC) are responsible for many of such reactions. The effect of cannabinoid is considered to be produced by an interaction between the compound and its endogenous specific/high-affinity receptors. Two subtypes of cannabinoid receptors (CB1 and CB2) have been identified and cloned. The CB1 receptor is distributed in central nervous system (CNS) regions including brain (Nature, Vol. 346, 1990, pp 561-564) while the CB2 receptor is distributed in immune system including spleen (Nature, Vol. 365, 1993, pp 61-65).
Substances having affinity to such cannabinoid receptors (agonists, antagonists or inverse agonists) may produce various pharmacological effects like marijuana. In particular, substances having affinity to central CB1 receptor may be useful for treatment of a CNS disease such as a psychotic disorder, a neurological disorder and the like.
Examples of the known substances having affinity to CB1 receptor include a 4,5-dihydro-1H-pyrazole compound (WO01/70700, WO03/026648, WO03/026647), a 1H-imidazole compound (WO03/027076, WO03/007887, WO03/063781, WO03/040107), a pyrazine compound (WO03/051850, WO03/051851), a 1H-pyrazole compound (U.S. Pat. No. 5,624,941, U.S. Pat. No. 6,509,367), a pyridine compound (WO03/084930, WO03/084943, WO03/082191), an azethidine compound (WO01/64632, WO03/020314), an arylamide compound (WO03/087027, WO03/082190), a 1,5,6,7-tetrahydropyrrolo[3,2-c]pyridine compound (WO03/027114), a pyrrole compound (WO03/027069) and a 1,2,4-triazole compound (WO03/082833). Meanwhile, JP1993-17434 discloses that specific pyrrolidine compounds such as 4-amino-5-chloro-N-[1-(diphenylmethyl)-5-(hydroxymethyl)-3-pyrrolidinyl]-2-methoxy-benzamide increased gastric motility in mice, but there are no suggestion on whether or not the pyrrolidine compound has an antagonistic activity against CB1 receptor.